Cancer-related fatigue (CRF) is reported by 30-80% of breast cancer survivors up to 10 years post-treatment. CRF can negatively impact quality of life (QOL) by reducing survivors' ability to participate in leisure activities, their capacity to sstain meaningful relationships, their ability to work, and their capacity to engage in social and other activities. Despite the high prevalence of CRF and its negative consequences, treatment options are limited. Pharmaceutical treatments have limited efficacy and side effects, while behavioral interventions have demonstrated efficacy but poor compliance. A nutritional supplementation intervention for the treatment of CRF in cancer survivors would be ideal due to easy implementation and a low incidence of side effects. Marine ?-3 Polyunsaturated Fatty Acids (PUFA), a popular nutritional supplement, may reduce CRF. Promising preliminary evidence from prospective observational studies in breast cancer survivors and small clinical trials in advanced cancer patients show marine ?-3 supplementation reduces CRF, possibly by reducing inflammatory responses. The primary aims of those clinical trials, however, were not to determine the effect of ?-3 supplementation on CRF, and they were not conducted in breast cancer survivors reporting CRF. To examine the effect of marine ?-3 supplementation in breast cancer survivors, it is imperative to 1) collect preliminary statistical data regarding their effec on CRF, 2) determine adherence and adverse events, and 3) collect preliminary statistical data on possible mechanisms of action to inform the design of future trials. The proposed randomized pilot trial, based upon both biological plausibility and preliminary data, is a three-arm study of two marine ?-3 supplementation regimens (1.7 g/day and 3.4 g/day) compared to placebo in 60 breast cancer survivors reporting CRF (self-reported CRF level e4 on a 0-10 scale). The proposed clinical trial aims to: 1) collect preliminary statistical data (mean changes and standard deviations) on two ?-3 supplementation regimens compared to placebo for reducing CRF, 2) determine the adherence and adverse events for the two ?-3 supplementation regimens compared to placebo, and 3) collect preliminary statistical data (mean changes and standard deviations) on two ?-3 supplementation regimens compared to placebo for reducing inflammation in breast cancer survivors. We hypothesize that preliminary statistical data will show marine ?-3 supplementation has a positive effect on CRF compared to placebo in fatigued breast cancer survivors and will help to accurately calculate statistical power for future trials. This trial would represent one of the first clinical trials to administer marine ?-3 supplements to breast cancer survivors reporting CRF and is designed to provide critical preliminary data to inform an anticipated R01 proposal. The R01 study will be a blinded, placebo-controlled, multicenter RCT that examines the effect of marine ?-3 supplementation on CRF in breast cancer survivors conducted through the University of Rochester Cancer Center Community Clinical Oncology Program (URCC CCOP).